Standardised Framework for Preclinical Translation of Paediatric Heart Valve Technologies

Abstract

Preclinical validation of heart valve (HV) prostheses requires large animal testing prior to human trials. While essential, current preclinical models lack standardisation—especially for paediatric applications, where ISO 5840 and regulatory guidance are limited, as noted by the Heart Valve Collaboratory. To address this, we reviewed existing large animal models used in translational HV research and propose a framework to standardise studies, improve consistency, and support the 3R policy, with a focus on HV prostheses for paediatric patients. A systematic literature review and consultation with clinicians, veterinarians and regulatory professionals was conducted, to compare ovine and porcine preclinical models, based on (1) their anatomical and developmental similarities of these animals to humans of different ages, (2) their suitability for replicating and studying specific HV defects and diseases and for testing of HV prostheses, and (3) animal specific limitations and advantages. The comparative analysis showed that ovine and porcine models are most commonly used. Pigs closely resemble the human cardiovascular anatomy and are preferred for HV disease research due to their pathophysiological similarities. Sheep, due to slower somatic growth, are widely used for testing of HV prostheses, however, their relevance to growing paediatric patients requires further scrutiny. Ethical, logistical, and economic considerations further influence model choice and standardisation efforts. A standardized framework for translational paediatric HV prostheses research will enhance study comparability, support translational efficinecy, and align with 3R policies. Stakeholder consenus and development of models that account for growth, are essential for paediatric HV research.